Simulating DNA behavior in microfluidic devices

Abstract

During most of the twentieth century, direct study of individual polymer molecules was impossible due to their small size. Therefore, polymers were typically studied in bulk solutions, and their behavior and interactions had to be understood through average bulk property measurements. Because the scale of most industrial applications greatly exceeded the size of these molecules, this level of analysis was satisfactory. In the last twenty years, however, the appearance of microfluidic devices, whose smallest length scales are comparable to the size of a polymer molecule, has offered ways to visually study the behavior of individual polymer molecules and made possible new and exciting applications that exploit the precise control afforded by the small size of these devices. One such application is gene mapping, which extracts, at a. coarse level, the information embedded in the base pair sequence of genomic DNA. This technology relies on the ability to manipulate single DNA molecules in order to perform such tasks as separating DNA based on length and stretching DNA away from its entropically coiled equilibrium state. Recently, many novel methods have been proposed to accomplish these tasks using microfabricated devices, and munch experimental work has been focused on identifying and characterizing the underlying physics governing these devices. Current understanding, however, is greatly hampered by the fact that experiments can only provide limited information about the behavior of DNA molecules (e.g., they are unable to resolve details on small time and length scales). Therefore, simulations are an invaluable tool in the study of DNA behavior in microfiuidic devices by complementing and guiding experimental investigations. In this thesis, we present Brownian Dynamics simulations of the single molecule behavior of DNA in microfluidic devices related to gene mapping. In particular, we have considered the use of a post array to "precondition" the configuration of molecules for subsequent stretching in a contraction and compared our results to previous experiments. We found good qualitative agreement between experiments and simulations for DNA behavior in the post array, but our simulations consistently overpredicted the final stretch of molecules at the end of the contraction, which we attributed to nonlinear electrokinetic effects. We also investigate the electrophoretic collision of a DNA molecule with a. large, ideally conducting post. Field-induced compression was shown to play a critical role in the escape process of a molecule trapped on the post surface, and an extensive theoretical analysis is performed, describing both the local field-induced compression and the larger collision problem. Finally, we study the relaxation process of an initially stretched molecule in slit-like confinement. We present the first simulation results that exhibit two distinct relaxation times in the linear force regime, as previously reported in recent experiments. Our analysis is focused on the experimentally inaccessible dynamics in the transverse directions, particularly at short times and on small length scales. Comparisons to the predictions of a recent mechanistic model of confined relaxation were found to be satisfactory.